Weiss Lauren A, Kosova Gülüm, Delahanty Ryan J, Jiang Lan, Cook Edwin H, Ober Carole, Sutcliffe James S
Department of Human Genetics, The University of Chicago, Chicago, IL, USA.
Eur J Hum Genet. 2006 Aug;14(8):923-31. doi: 10.1038/sj.ejhg.5201644. Epub 2006 May 17.
Autism is a pervasive developmental disorder affecting more males than females. Heritability estimates for autism can rise above 90%, and genes influencing the serotonin system are strong candidates for autism susceptibility genes, as drugs selectively acting on the serotonin system are some of the most effective treatments for maladaptive behaviors seen in autism. ITGB3 was recently identified as a male quantitative trait locus (QTL) for whole-blood serotonin levels in the Hutterites (P = 0.0003). Here, we demonstrate associations between variation in ITGB3 and serotonin levels in two outbred samples (P = 0.010 and 0.015). Lastly, we show that a coding variant of ITGB3 is associated with autism susceptibility in a large multiplex sample (P = 0.00082), and that this variation has different effects in males and females (P = 0.0018).
自闭症是一种广泛性发育障碍，男性患者多于女性。自闭症的遗传率估计可超过90%，影响血清素系统的基因是自闭症易感基因的有力候选者，因为选择性作用于血清素系统的药物是治疗自闭症中出现的适应不良行为最有效的药物之一。整合素β3（ITGB3）最近被确定为哈特人全血血清素水平的男性数量性状位点（QTL）（P = 0.0003）。在此，我们在两个远交样本中证明了ITGB3变异与血清素水平之间的关联（P = 0.010和0.015）。最后，我们表明ITGB3的一个编码变异与一个大型多位点样本中的自闭症易感性相关（P = 0.00082），并且这种变异在男性和女性中具有不同的影响（P = 0.0018）。
